title: Improvement of functional recovery of donor heart following cold static storage with doxycycline cardioplegia.
abstract: Injury to the donor heart during cold preservation has a negative impact on graft survival before transplantation. This study aims to examine whether doxycycline, known as an MMP-2 inhibitor, has a positive effect on donor heart preservation via its antioxidant action when added to standard preservation solution. Hearts were obtained from 3-month-old male Wistar rats and randomly divided into three groups: hearts stored for 1 h at 4 °C (1) with doxycycline preservation solution (DOX cardioplegia) with low Ca(2+); (2) with standard cardioplegia with low Ca(2+); and (3) unstored hearts. All hearts were perfused in working mode, arrested at 37 °C, removed from the perfusion system, reattached in Langendorff perfusion system, and converted to working mode for 1 h. At the end of the storage period, hearts preserved in DOX cardioplegia had significantly less weight gain than those preserved in the standard cardioplegia. DOX cardioplegia-induced preservation resulted in significantly higher heart rates and better recovery quality during reperfusion in aortic flow compared to the standard cardioplegia group. Recovery in the left ventricular function and Lambeth Convention Arrhythmia scores during 1 h reperfusion were also significantly better in the DOX cardioplegia group. Biochemical data showed that DOX cardioplegia prevented an increase in MMP-2 activity and blocked apoptosis through increased activity of the pro-survival kinase Akt in the donor heart homogenates. DOX cardioplegia also led to a balanced oxidant/antioxidant level in the heart homogenates. This is the first study to report that cardioplegia solution containing doxycycline provides better cardioprotection via the preservation of heart function, through its role in controlling cellular redox status during static cold storage.
authors.affiliation: Department of Cardiovascular Surgery, Ankara Diskapi Training and Research Hospital, Ministry of Health, 06330, Ankara, Turkey.
authors.forename: Evren
authors.initials: E
authors.lastname: Ozcinar
authors.forename: Esma N
authors.initials: EN
authors.lastname: Okatan
authors.forename: Erkan
authors.initials: E
authors.lastname: Tuncay
authors.forename: Sadik
authors.initials: S
authors.lastname: Eryilmaz
authors.forename: Belma
authors.initials: B
authors.lastname: Turan
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002314:Cardioplegic Solutions / Q000494:pharmacology*; D050377:Cold Ischemia / Q000009:adverse effects; D003080:Cold Temperature; D019610:Cytoprotection; D004318:Doxycycline / Q000494:pharmacology*; D006324:Heart Arrest, Induced / Q000009:adverse effects; D016027:Heart Transplantation / Q000379:methods*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function; D013997:Time Factors; D020858:Tissue and Organ Harvesting / Q000009:adverse effects / Q000379:methods*; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000975:Antioxidants; D002314:Cardioplegic Solutions; D051057:Proto-Oncogene Proteins c-akt; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D004318:Doxycycline